Vegfb gene knockout mice display reduced pathology and synovial angiogenesis in both antigen‐induced and collagen‐induced models of arthritis

作者：Arne W. Mould, Ian D. Tonks, Marian M. Cahill, Allison R. Pettit, Ranjeny Thomas, Nicholas K. Hayward, Graham F. Kay · 发表于：Arthritis & Rheumatism · 年份：2003 · DOI：10.1002/art.11232 · 被引用次数：136 · 研究领域：Rheumatoid Arthritis Research and Therapies、Angiogenesis and VEGF in Cancer、Immune cells in cancer

OBJECTIVE: To determine the role of vascular endothelial growth factor B (VEGF-B) in 2 mouse models of arthritis, antigen-induced arthritis (AIA) and collagen-induced arthritis (CIA). METHODS: For AIA studies, monarticular AIA was induced by methylated bovine serum albumin (mBSA) priming of Vegfb gene knockout (Vegfb(-/-)) and wild-type (Vegfb(+/+)) mice, followed by intraarticular injection of mBSA or saline control 8 days later. CIA was induced in Vegfb(-/-) and Vegfb(+/+) mice by intradermal injection of chick type II collagen in adjuvant. Arthritis was monitored in both models using defined criteria (clinical and histologic). Angiogenesis was measured by synovial vessel density in diseased and control joints. RESULTS: In AIA studies, Vegfb(+/+) mice displayed significant knee joint swelling and synovial inflammation 7 days after intraarticular injection of antigen. Synovial inflammation was associated with angiogenesis, since vessel density in AIA synovium was significantly higher in arthritic than in control joints from the same animal. Knee joint swelling, synovial inflammation, and inflammation-associated vessel density in arthritic joints were reduced in Vegfb(-/-) mice compared with arthritic joints from Vegfb(+/+) mice. Similarly, in CIA, both disease incidence and mean clinical severity scores were significantly reduced in Vegfb(-/-) mice compared with Vegfb(+/+) mice. Mean histologic severity scores and mean synovial vessel density were reduced in diseased joints ...